Toxic Effects of Antineoplastic Therapy in Patients Breast Cancer in Caruaru-PE Oncology Center

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Toxic effects of antineoplastic therapy in patients breast cancer in Caruaru-PE oncology center Efectos tóxicos de la terapia antineoplásica en pacientes cáncer de mama en el centro de oncología Caruaru-PE Rayssa Almeida Carneiro1, Ana Caroline de Brito França1, Sabryna Aleadynah Barbosa da Silva1, Iago Dillion Lima Cavalcanti1, Analúcia Guedes Silveira Cabral1 and Adrya Lucia Peres1 1 University Center Tabosa of Almeida – ASCES/UNITA, Caruaru, Pernambuco, Brazil

http://dx.doi.org/10.30827/ars.v59i4.8113 Artículo Original ABSTRACT Original Article Objective: to evaluate the main clinical symptoms associated with the toxic effects of antineoplastic therapy in women with breast cancer at a cancer treatment center in the city of Caruaru/PE. Correspondencia Correspondence Methods: This is an analytical and transversal study with a quantitative approach, carried out between Iago Dillion Lima Cavalcanti, September and December 2017, whose data source was the medical records of the patients included in Specialist in Cancer Attention and the study. Palliative Care, University Center Tabosa of Almeida - ASCES/UNITA, Caruaru, Results: the majority of the sample consisted of women aged between 41 and 50 years (28.6%). This Pernambuco, Brazil study made it possible to identify the most frequent histological type of breast cancer, with invasive e-mail: [email protected] ductal carcinoma observed in 88.6% and the most used protocol was Doxorubicin, Cyclophosphamide

Financiación and Paclitaxel. Alopecia (91.4%) was the main adverse event observed in patients. Fundings Conclusion: it was possible to verify that the observation of these effects, allows a better control during No fundings received the therapy, enabling improvement of the time and quality of life.

Conflicto de interés Keywords: Antineoplastic Agents; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Competing interest Cancer; Medical oncology. None daclared

RESUMEN Received: 02.11.2018 Accepted: 27.11.2018 Objetivo: evaluar los principales síntomas clínicos asociados con los efectos tóxicos de la terapia an- tineoplásica en mujeres con cáncer de mama en un centro de tratamiento del cáncer en la ciudad de Caruaru/PE.

Métodos: este es un estudio analítico y transversal con un enfoque cuantitativo, realizado entre septiem- bre y diciembre de 2017, cuya fuente de datos fueron las historias clínicas de los pacientes incluidos en el estudio.

Resultados: la mayor parte de la muestra estuvo formada por mujeres de 41 a 50 años (28,6%). Este estudio permitió identificar el tipo histológico más frecuente de cáncer de mama, con un carcinoma ductal invasivo observado en el 88,6% y el protocolo más utilizado fue la doxorubicina, la ciclofosfamida y el paclitaxel. La alopecia (91,4%) fue el principal evento adverso observado en los pacientes.

Conclusión: fue posible verificar que la observación de estos efectos permite un mejor control durante la terapia, lo que permite mejorar el tiempo y la calidad de la vida.

Palabras clave: Antineoplásicos; Neoplasias de la Mama; Efectos Colaterales y Reacciones Adversas Re- lacionados con Medicamentos; Oncología Médica.

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Ars Pharm. 2018; 59(4): 221-226 221 Almeida Carneiro R, et al.

INTRODUCTION cancer at a cancer treatment center in the city of Caruaru/ PE. Breast cancer is the most common among women in the world and in Brazil, accounting for about 25% of new cases METHODS per year, the estimated number of new cases for the year This is an analytical and cross-sectional quantitative study, 2016 is 57,960. Breast cancer may also be present in men; carried out between September and December 2017 in an however, it is very rare, accounting for only 1% of the total oncology center, located in the city of Caruaru/PE. Data cases of the disease. Relatively rare before age 35, breast collection was performed through a questionnaire with the cancer increases its incidence proportionally with advanc- following variables: age, tumor histological type, chemo- ing age, especially after age 50(1). therapy protocol and cycle. The undesirable effects present- Mammary neoplasia is a pathology feared today, especially ed by the patients during the chemotherapy treatment were by women. It is commonly associated with physical muti- also identified through the analysis of the medical records lation, changes in style and quality of life, and despite the and the patient reports. technological advancement in health in relation to treat- Included in the study were all women diagnosed with ment and the increase in mass-mediated information, neo- breast cancer treated during the study period who were plasia rates are high worldwide, in the that it is Brazil gen- older than 20 years and who were taking antineoplastic erally the disease is diagnosed in advanced stages, making therapy. On the other hand, women who underwent radia- treatment difficult(2). tion therapy and patients who abandoned chemotherapeu- When breast cancer is diagnosed, the patient will undergo tic treatment were excluded. a combination of treatments, including surgery, radiation The information obtained through the data collection was therapy, chemotherapy and hormone therapy, as well as organized and analyzed through descriptive statistical possible unconventional treatments for her physical and techniques through absolute distributions, percentage of mental well-being(3). measures and techniques of inferential statistics. The soft- The main goal of antineoplastic chemotherapy is to destroy ware used was EpiData and Microsolft® Office Excel 2013. the cancer cells while preserving the normal ones. How- Ethical approval ever, many chemotherapeutic agents act in a non-specific way, damaging both malignant and normal cells of rapid All procedures performed in studies involving human par- division, such as gastrointestinal, capillary and immune ticipants were performed under an approved protocol and systems, leading to side effects of chemotherapy such as: in accordance with the ethical standards of the Institutional nausea, hair loss and greater susceptibility infections. In Research Committee of Caruaruense Association of Higher addition, the fact that the biochemical and morphological Education and Technical (Approval No. 2.158.459) and with differences of normal and malignant cells are minimal there the 1964 Helsinki Declaration and its later amendments or is a difficulty in the immune response on top of these cells comparable ethical standards. and this facilitates their growth so that they develop resist- ance to antineoplastics rapidly(4). RESULTS

The antineoplastic agents most employed in the treatment The study consisted of 35 female patients on antineoplas- of cancer include polyfunctional alkylants, antimetabo- tic chemotherapy. According to table 1, the age group with lites, antitumor antibiotics, mitotic inhibitors and the like. the highest number of patients was 41-50 years (28.6%), fol- New drugs are being permanently isolated and applied lowed by patients aged between 51 and 60 years (22.9%). experimentally in animal models before they are used in In the histological classification of cancer, we highlight the humans(5). invasive ductal carcinoma, 31 women (88.6%), followed by lobular carcinoma, three women (8.6%) and lastly other A better knowledge of the adverse effects in response to dif- types of cancer, one woman (2.9%). It was also verified that ferent protocols commonly used in antineoplastic therapy about 23% of the patients had hypertension and 8.6% had of breast cancer will allow a better definition of the main diabetes. effects presented, thus allowing the development of strate- gies and behaviors that minimize these effects, improving As shown in Figure 1, the protocols most used by the study the patient quality of life. The objective of this study was patients were as follows: Doxorubicin, Cyclophosphamide to evaluate the main clinical symptoms associated with the and Paclitaxel (28.57%), Paclitaxel (11.42%), Anastrozole toxic effects of antineoplastic therapy in women with breast and Paclitaxel and Carboplatin (8.57%).

222 Ars Pharm. 2018; 59(4): 221-226 Toxic effects of antineoplastic therapy in patients breast cancer in Caruaru-PE oncology center

Table 1: Absolute and relative frequency of patients diagnosed Table 3 shows the association of the protocols most used by with breast cancer at a cancer treatment center by age group (in the patients and the adverse events presented by them dur- years), histological type of cancer and chronic diseases. Caruaru, Pernambuco, Brazil, 2017, (n = 35). ing the study period. It was observed that 29.6% of the patients who used the protocol Doxorubicin, Cyclophospha- n (absolute % (relative mide and Paclitaxel (AC-T) presented alopecia, in contrast frequency) frequency) to the patients using the protocols with Paclitaxel (Tx) and Age group (years) Paclitaxel + Carboplatin (Tx + CBP), only 17.4% and 14.3%, respectively, presented with alopecia. 20 - 30 1 2.9

31 – 40 7 20.0 Table 2: Absolute and relative frequency of adverse events presented by patients undergoing chemotherapy. Caruaru, Pernam- 41 – 50 10 28.6 buco, Brazil, 2017 (n = 35). 51 – 60 8 22.9 n (absolute % (relative Adverse event 61 – 70 6 17.1 frequency) frequency)

80 years or more 3 8.6 Taste change 18 51.4

Histological Type Alopecia 32 91.4 Invasive Ductal Carci- 31 88.6 Nauseas 30 85.7 noma Vomiting 24 68.6 Carcinoma Lobular 3 8.6 Decreased appetite 15 42.9 Others 1 2.9 Dizziness 10 28.6 Comorbidities Physical tiredness 23 65.7 Arterial hypertension 8 22.9 Somnolence 10 28.6 Diabetes 3 8.6 Source: Research data Source: Research data

Table 3: Absolute and relative frequency of association of protocols and adverse events presented by patients diagnosed with breast cancer in an antineoplastic treatment clinic. Caruaru, Pernambuco, Brazil, 2017.

AC-T Paclitaxel Tx+CBP

Taste change 2 (7.4%) 2 (7.4%) 3 (10.7%)

Alopecia 8 (29.6%) 3 (13%) 4 (14.3%)

Nauseas 5 (18.5%) 4 (14.3%) 4 (14.3%)

Vomiting 5 (18.5%) 2 (7.4%) 4 (14.3%)

Decreased 2 (7.4%) 1 (4.3%) 4 (14.3%) appetite

Dizziness - 1 (4,3%) 3 (10.7%)

Physical 4 (14.3%) 3 (13%) 4 (14.3%) tiredness

Somnolence 1 (3.7%) 2 (8.7%) 2 (7.1%)

Figure 1: Relative frequency of protocols used by patients under- Legend: AC-T: Doxorubicin, Cyclophosphamide and Paclitaxel; going chemotherapy. Caruaru, Pernambuco, Brazil, 2017 (n= 35). Tx: Paclitaxel; Tx+CBP: Paclitaxel and Carboplatin. Source: Research data.

The main adverse events observed in the patients during During the research, alopecia was the most frequent ab- chemotherapy were alopecia (91.4%), nausea (85.7%) and solute and relative adverse event in all cycles studied, as vomiting (68.6%), as observed in Table 2. shown in table 4.

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Table 4: Association of Time (Cycle) with the adverse events presented by the patients diagnosed with breast cancer and in antineoplastic treatment. Caruaru, Pernambuco, Brazil, 2017.

Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 Cycle 7 Cycle 8 Cycle 11

1 1 Taste change 5 (27.7%) 3 (16.7%) 5 (27.7%) 1 (5.6%) 2 (11.1%) - (5.6%) (5.6%)

Alopecia 5 (15.6%) 10 (31.25%) 4 (12.5%) 2 (6.25%) 6 (18.75%) 1 (3.12%) 3 (9.37%) 1 (3.12%)

9 6 1 3 1 Nauseas 5 (16.67%) 4 (13.33%) 1 (3.33%) (30%) (20%) (3.33%) (10%) (3.33%)

Vomiting 2 (8.33%) 10 (41.67%) 4 (16.67%) 1 (4.17%) 3 (12.5%) 1 (4.17%) 2 (8.33%) 1 (4.17%)

Decreased ap- 3 2 (13.33%) 4 (26.67%) 1 (6.67%) 2 (13.33%) - 2 (13.33%) 1 (13.33%) petite (20%)

4 1 1 2 2 Dizziness - - - (40%) (10%) (10%) (20%) (20%)

Physical tired- 3 (13.04%) 8 (34.78%) 2 (8.69%) 1 (4.35%) 5 (21.74%) - 3 (13.04%) 1 (4.35%) ness

2 1 1 5 1 Somnolence - - - (20%) (10%) (10%) (50%) (10%)

Source: Research data

DISCUSSION the study period. The same result was obtained in the research carried out in a general, university and public hos- In this study, it was possible to observe that the age group pital, in the hematology-oncology outpatient clinic, located from 41 to 50 years (28.6%) was the most incident, which in the State of Paraná, whose hospital attendance is solely confirms with another study carried out in the cityof by SUS(10). Ribeirão Preto, located in the state of São Paulo, where there Chemotherapy brings with it several commonly expected was a predominance of age between 41-50 years (40.9%)(6). adverse effects during treatment, such as: nausea, vomiting, The most common histological type was Invasive Ductal diarrhea or constipation, alopecia, among others. It is nec- Carcinoma (88.6%), presenting similarity to a retrospec- essary to evaluate the cost-benefit of each treatment, since tive epidemiological and descriptive study conducted at the answers are individualized and requires a timely and the Crato Specialty Center, Ceará (77%)(7). Another study effective intervention to minimize them(11). Among these conducted between 2000 and 2009 observed that the most adverse events, alopecia (91.4%), nausea (85.7%), vomiting frequent tumor histology among the included patients was (68.6%) and physical fatigue (65.7%) were the ones with the the Invasive Ductal Carcinoma with 90.7%(8). highest rates in this study.

A survey of 285 individuals diagnosed with some form of A total of 91.4% of the women had alopecia, which is de- cancer concluded that 45% of the patients were hyperten- fined as the loss of hair and any other body hair such as the sive and 14.03% declared themselves diabetic. This result eyebrows, the axillary, pubic hair and/or the legs and arms. is in agreement with what was found in this study, since This side effect occurs after one to two weeks of the onset the prevalence of systemic arterial hypertension (23%) was of chemotherapy and is due to the lack of hair production higher than that of diabetes mellitus (8.6%). It is important or thinning caused by the abrupt interruption of the mitotic to highlight that these chronic diseases have negatively activity of the capillary matrix, which leads to the weaken- interfered in the quality of life of individuals affected by ing of the capillary shaft causing the hair to fall during the these diseases, as well as their great economic impact to the act of combing, hair washing or even handling. Hair loss Unified Health System (SUS), considering the high sums becomes more pronounced about one to two months after allocated for prevention, health promotion, to the treat- starting chemotherapy and, with repeated cycles of it, can ment and recovery of these pathologies and their compli- lead to total alopecia(12). cations(9). Among the gastrointestinal adverse events we may men- The AC-T protocol (Doxorubicin, Cyclophosphamide and tion nausea, vomiting, mucositis, diarrhea, anorexia, sto- Paclitaxel) was the most used among the patients during matitis, discomfort or abdominal pain, but those referred

224 Ars Pharm. 2018; 59(4): 221-226 Toxic effects of antineoplastic therapy in patients breast cancer in Caruaru-PE oncology center by cancer patients as the most stressful and uncomfortable it will be possible to better care for women’s health and a are nausea and vomiting. They occur together or isolated, qualified and humanized care. however they must be evaluated separately, because they are distinct events, with also different causes. In a study of REFERENCES 79 women aged 29 to 69 years, 93% had nausea and 87% had vomiting(13). 1. Brazil. Ministry of Health. National Cancer Institute – INCA. Câncer de Mama. Available in: http://www2.inca.gov.br/ The literature draws attention to the fatigue symptom, since wps/wcm/connect/tiposdecancer/site/home/mama. Ac- it can directly interfere with women’s emotional well-being cess in: Feb 20, 2018. and quality of life. The caveat is for health care profession- 2. Garcia SN, Jacowski M, Castro GC, Galdino C, Guimarães als who must be prepared and alert to guide patients by PRB, Kalinke LP . Quality of life domains aff ected in wom- helping them recognize fatigue and clarifying appropriate en with breast cancer. Rev Gaúcha Enferm. 2015;36:89-96. (11) ways to relieve this symptom . doi:10.1590/1983-1447.2015.02.45718.

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